Tandem cDNAs encoding chemokines CC-1, CC-2, and CC-3

Abstract

The CC type chemokines belong to a family of polypeptides which have proven to be mediators of immune reactions, and they have recently attracted attention due to their antiviral activity with respect to HIV. The cloning and molecular characterization of a human tandem gene is disclosed which contains the closely linked coding regions for two new CC type chemokines the sequences of which are highly homologous with that of MIP-1α. The transcription of the tandem gene leads to a bicistronic mature transcript which contains the non-overlapping open reading frames for the recently described factor HCC-1 and an as yet unknown CC type chemokine, designated as CC-2. Moreover, alternative splicing of the primary transcript yields at least one additional CC type chemokine, cytokine CC-3. Two functional promoter regions were identified within the tandem gene. The disclosed data provide some basic knowledge about the structure and expression of the new human CC-2/HCC-1 tandem gene and describe a mechanism according to which the coexpression of closely linked genes could be regulated in higher eucaryotes.

What is claimed is:  
     
       1. An isolated nucleic acid molecule comprising a nucleotide sequence encoding the amino acid sequence of chemokine CC-2 as shown in SEQ ID NO: 6. 
     
     
       2. A nucleic acid molecule according to claim  1 , comprising the nucleotide sequence shown in SEQ ID NO: 3. 
     
     
       3. An isolated nucleic acid molecule comprising a nucleotide sequence encoding the amino acid sequence of chemokine CC-3 as shown in SEQ ID NO: 12. 
     
     
       4. A nucleic acid molecule according to claim  3 , comprising the nucleotide sequence as shown in SEQ ID NO: 9. 
     
     
       5. An isolated bicistronic nucleic acid molecule comprising nucleotide sequences encoding the amino acid sequence of chemokine CC-2 as shown in SEQ ID NO: 6 and the amino acid sequence of chemokine CC-3 as shown in SEQ ID NO: 12. 
     
     
       6. A nucleic acid molecule according to claim  5 , comprising the nucleotide sequence shown in SEQ ID NO: 10. 
     
     
       7. A nucleic acid molecule according to claim  6 , comprising the nucleotide sequence shown in SEQ ID NO: 2. 
     
     
       8. An isolated bicistronic nucleic acid molecule comprising nucleotide sequences encoding the amino acid sequence of chemokine CC-2 as shown in SEQ ID NO: 6 and the amino acid sequence of chemokine CC-1 as shown in SEQ ID NO: 7. 
     
     
       9. A nucleic acid molecule according to claim  8 , comprising the nucleotide sequence shown in SEQ ID NO: 5. 
     
     
       10. A nucleic acid molecule according to claim  9 , comprising the nucleotide sequence shown in SEQ ID NO: 1. 
     
     
       11. An isolated chemokine CC-2 polypeptide comprising the amino acid sequence shown in SEQ ID NO: 6 or an amidated, acetylated, phosphorylated, or glycosylated derivative thereof. 
     
     
       12. An isolated chemokine CC-3 polypeptide comprising the amino acid sequence shown in SEQ ID NO: 12 or an amidated, acetylated, phosphorylated, or glycosylated derivative thereof. 
     
     
       13. A pharmaceutical composition comprising a chemokine polypeptide according to claim  11  and a pharmaceutically acceptable carrier. 
     
     
       14. A pharmaceutical composition comprising a chemokine polypeptide according to claim  12  and a pharmaceutically acceptable carrier. 
     
     
       15. A pharmaceutical composition comprising chemokine CC-2 and CC-3 polypeptides, wherein 
       the CC-2 polypeptide comprises the amino acid sequence shown in SEQ ID NO: 6 or is an amidated, acetylated, phosphorylated, or glycosylated derivative thereof; and  
       the CC-3 polypeptide comprises the amino acid sequence shown in SEQ ID NO: 12 or is an amidated, acetylated, phosphorylated, or glycosylated derivative thereof.